Anti-LINGO-1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice

作者全名："Yang, Hao; Jiang, Lin; Zhang, Yi; Liang, Xin; Tang, Jing; He, Qi; Luo, Yan-Min; Zhou, Chun-Ni; Zhu, Lin; Zhang, Shan-Shan; Xiao, Kai; Zhu, Pei-Lin; Wang, Jin; Li, Yue; Chao, Feng-Lei; Tang, Yong"

作者地址："[Yang, Hao; Tang, Jing; He, Qi; Zhou, Chun-Ni; Zhu, Lin; Zhang, Shan-Shan; Xiao, Kai; Zhu, Pei-Lin; Wang, Jin; Li, Yue; Chao, Feng-Lei; Tang, Yong] Chongqing Med Univ, Coll Basic Med, Dept Histol & Embryol, Chongqing, Peoples R China; [Yang, Hao; Tang, Jing; He, Qi; Zhou, Chun-Ni; Zhu, Lin; Zhang, Shan-Shan; Xiao, Kai; Zhu, Pei-Lin; Wang, Jin; Li, Yue; Chao, Feng-Lei; Tang, Yong] Chongqing Med Univ, Coll Basic Med, Lab Stem Cell & Tissue Engn, Chongqing, Peoples R China; [Yang, Hao] Chongqing Med Univ, Coll Biomed Engn, Dept Biomed Engn, Chongqing, Peoples R China; [Jiang, Lin] Chongqing Med Univ, Expt Teaching Management Ctr, Chongqing, Peoples R China; [Zhang, Yi] Chongqing Med Univ, Dept Lab Med, Chongqing, Peoples R China; [Liang, Xin] Chongqing Med Univ, Coll Basic Med, Dept Pathophysiol, Chongqing, Peoples R China; [Luo, Yan-Min] Chongqing Med Univ, Dept Physiol, Chongqing, Peoples R China"

通信作者："Chao, FL; Tang, Y (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Histol & Embryol, Chongqing, Peoples R China.; Chao, FL (通讯作者)，Chongqing Med Univ, Coll Basic Med, Lab Stem Cell & Tissue Engn, Chongqing, Peoples R China."

来源：JOURNAL OF COMPARATIVE NEUROLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000747597900001

JCR分区：Q1

影响因子：2.5

年份：2022

卷号：530

期号：10

开始页：1606

结束页：1621

文献类型：Article

关键词：Alzheimer's disease; anti-LINGO-1 antibody; cognitive abilities; hippocampus; oligodendrocytes

摘要："Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti-LINGO-1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO-1. In this study, we aim to assess the effect of anti-LINGO-1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10-month-old male amyloid-beta (A beta) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti-LINGO-1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y-maze tests, and A beta deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti-LINGO-1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO-1 positive cells, decreased A beta deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO-1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO-1 can alleviate cognitive deficits in APP/PS1 mice and decrease A beta deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO-1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO-1 might be a potential therapeutic strategy for AD."

基金机构："National Natural Science Foundation of China [81801269, 81871073, 82002227]; Natural Science Foundation of Chongqing, P. R. China [cstc2020jcyj-msxmX0125]"

基金资助正文："National Natural Science Foundation of China, Grant/Award Numbers: 81801269, 81871073, 82002227; the Natural Science Foundation of Chongqing, P. R. China, Grant/Award Number: cstc2020jcyj-msxmX0125"